This invention is in the general field of testing for mutagenic activity.
Non-natural substances or compositions are often tested for their mutagenic potential because of the high correlation between mutagenic activity and carcinogenic activity. Furthermore, there is also the expectation that compounds with antimutagenic activity would be beneficial in the prevention of cancers. Several methods and assays have therefore been developed to determine the mutagenic or antimutagenic activity of substances in bacteria, yeast, animal cell cultures and whole animals. For example, the Ames test or variants thereof is widely used as a test of bacterial mutagenicity [Ames et al. (1973) Proc. Natl. Acad. Sci. USA 70:782-786; McCann et al. (1975) Proc. Natl. Acad. Sci. USA 72:5135-5139; Maron and Ames (1983) Mutat. Res. 113:173-215].
In the past few years, it has been recognized that mutations can arise not only in dividing cells in the course of replication of the genetic material or in the course of repair following to the genetic material, but that they can also arise in populations of essentially nondividing cells. There is also evidence that the mechanism by which mutations arise in nondividing cells are different from those in dividing cells [reviewed in Foster (1993) Annu. Rev. Microbiol., 47:467-504; Rosenberg et al. (1995) Mol. Microbiol. 18:185-189].